The present invention relates to the delivery of antihistamines through an inhalation route. Specifically, it relates to aerosols containing antihistamines that are used in inhalation therapy.
There are a number of antihistamine containing compositions currently marketed for the treatment of allergy symptoms. The compositions contain at least one active ingredient that provides for observed therapeutic effects. Among the active ingredients in such compositions are azatadine, brompheniramine, carbinoxamine, chlorpheniramine, clemastine, cyproheptadine, loratadine, pyrilamine, hydroxyzine, and promethazine.
It is desirable to provide a new route of administration for antihistamines that rapidly produces peak plasma concentrations of the compound. The provision of such a route is an object of the present invention.
The present invention relates to the delivery of antihistamines through an inhalation route. Specifically, it relates to aerosols containing antihistamines that are used in inhalation therapy.
In a composition aspect of the present invention, the aerosol comprises particles comprising at least 5 percent by weight of an antihistamine. Preferably, the particles comprise at least 10 percent by weight of an antihistamine. More preferably, the particles comprise at least 20 percent, 30 percent, 40 percent, 50 percent, 60 percent, 70 percent, 80 percent, 90 percent, 95 percent, 97 percent, 99 percent, 99.5 percent or 99.97 percent by weight of an antihistamine.
Typically, the antihistamine is not one of the following antihistamines: dexmedetomidine, diphenhydramine, doxylamine, loratidine, and promethazine.
Typically, the aerosol has a mass of at least 0.10 xcexcg. Preferably, the aerosol has a mass of at least 100 xcexcg. More preferably, the aerosol has a mass of at least 200 xcexcg.
Typically, the aerosol particles comprise less than 10 percent by weight of antihistamine degradation products. Preferably, the particles comprise less than 5 percent by weight of antihistamine degradation products. More preferably, the particles comprise less than 2.5, 1, 0.5, 0.1 or 0.03 percent by weight of antihistamine degradation products.
Typically, the aerosol particles comprise less than 90 percent by weight of water. Preferably, the particles comprise less than 80 percent by weight of water. More preferably, the particles comprise less than 70 percent, 60 percent, 50 percent, 40 percent, 30 percent, 20 percent, 10 percent, or 5 percent by weight of water.
Typically, at least 50 percent by weight of the aerosol is amorphous in form, wherein crystalline forms make up less than 50 percent by weight of the total aerosol weight, regardless of the nature of individual particles. Preferably, at least 75 percent by weight of the aerosol is amorphous in form. More preferably, at least 90 percent by weight of the aerosol is amorphous in form.
Typically, the aerosol has an inhalable aerosol particle density greater than 106 particles/mL. Preferably, the aerosol has an inhalable aerosol particle density greater than 107 particles/mL. More preferably, the aerosol has an inhalable aerosol particle density greater than 108 particles/mL.
Typically, the aerosol particles have a mass median aerodynamic diameter of less than 5 microns. Preferably, the particles have a mass median aerodynamic diameter of less than 3 microns. More preferably, the particles have a mass median aerodynamic diameter of less than 2 or 1 micron(s).
Typically, the geometric standard deviation around the mass median aerodynamic diameter of the aerosol particles is less than 3.0. Preferably, the geometric standard deviation is less than 2.85. More preferably, the geometric standard deviation is less than 2.7.
Typically, the aerosol is formed by heating a composition containing an antihistamine to form a vapor and subsequently allowing the vapor to condense into an aerosol.
In another composition aspect of the present invention, the aerosol comprises particles comprising at least 5 percent by weight of azatadine, brompheniramine, carbinoxamine, chlorpheniramine, clemastine, cyproheptadine, loratadine, pyrilamine, hydroxyzine, or promethazine. Preferably, the particles comprise at least 10 percent by weight of azatadine, brompheniramine, carbinoxamine, chlorpheniramine, clemastine, cyproheptadine, loratadine, pyrilamine, hydroxyzine, or promethazine. More preferably, the particles comprise at least 20 percent, 30 percent, 40 percent, 50 percent, 60 percent, 70 percent, 80 percent, 90 percent, 95 percent, 97 percent, 99 percent, 99.5 percent or 99.97 percent by weight of azatadine, brompheniramine, carbinoxamine, chlorpheniramine, clemastine, cyproheptadine, loratadine, pyrilamine, hydroxyzine, or promethazine.
Typically, the aerosol has a mass of at least 0.10 xcexcg. Preferably, the aerosol has a mass of at least 100 xcexcg. More preferably, the aerosol has a mass of at least 200 xcexcg.
Typically, the aerosol particles comprise less than 10 percent by weight of azatadine, brompheniramine, carbinoxamine, chlorpheniramine, clemastine, cyproheptadine, loratadine, pyrilamine, hydroxyzine, or promethazine degradation products. Preferably, the particles comprise less than 5 percent by weight of azatadine, brompheniramine, carbinoxamine, chlorpheniramine, clemastine, cyproheptadine, loratadine, pyrilamine, hydroxyzine, or promethazine degradation products. More preferably, the particles comprise less than 2.5, 1, 0.5, 0.1 or 0.03 percent by weight of azatadine, brompheniramine, carbinoxamine, chlorpheniramine, clemastine, cyproheptadine, loratadine, pyrilamine, hydroxyzine, or promethazine degradation products.
Typically, the aerosol particles comprise less than 90 percent by weight of water. Preferably, the particles comprise less than 80 percent by weight of water. More preferably, the particles comprise less than 70 percent, 60 percent, 50 percent, 40 percent, 30 percent, 20 percent, 10 percent, or 5 percent by weight of water.
Typically, at least 50 percent by weight of the aerosol is amorphous in form, wherein crystalline forms make up less than 50 percent by weight of the total aerosol weight, regardless of the nature of individual particles. Preferably, at least 75 percent by weight of the aerosol is amorphous in form. More preferably, at least 90 percent by weight of the aerosol is amorphous in form.
Typically, where the aerosol comprises azatadine, the aerosol has an inhalable aerosol drug mass density of between 0.2 mg/L and 2.5 mg/L. Preferably, the aerosol has an inhalable aerosol drug mass density of between 0.35 mg/L and 2 mg/L. More preferably, the aerosol has an inhalable aerosol drug mass density of between 0.5 mg/L and 1.5 mg/L.
Typically, where the aerosol comprises clemastine, the aerosol has an inhalable aerosol drug mass density of between 0.25 mg/L and 6 mg/L. Preferably, the aerosol has an inhalable aerosol drug mass density of between 0.35 mg/L and 4 mg/L. More preferably, the aerosol has an inhalable aerosol drug mass density of between 0.5 mg/L and 3.5 mg/L.
Typically, where the aerosol comprises chlorpheniramine, the aerosol has an inhalable aerosol drug mass density of between 0.5 mg/L and 5 mg/L. Preferably, the aerosol has an inhalable aerosol drug mass density of between 0.75 mg/L and 4 mg/L. More preferably, the aerosol has an inhalable aerosol drug mass density of between 1 mg/L and 3 mg/L.
Typically, where the aerosol comprises brompheniramine, carbinoxamine or cyproheptadine, the aerosol has an inhalable aerosol drug mass density of between 0.8 mg/L and 10 mg/L. Preferably, the aerosol has an inhalable aerosol drug mass density of between 1.4 mg/L and 8 mg/L. More preferably, the aerosol has an inhalable aerosol drug mass density of between 2 mg/L and 6 mg/L.
Typically, where the aerosol comprises loratadine, the aerosol has an inhalable aerosol drug mass density of between 2 mg/L and 25 mg/L. Preferably, the aerosol has an inhalable aerosol drug mass density of between 3.5 mg/L and 20 mg/L. More preferably, the aerosol has an inhalable aerosol drug mass density of between 5 mg/L and 15 mg/L.
Typically, where the aerosol comprises promethazine, the aerosol has an inhalable aerosol drug mass density of between 5 mg/L and 60 mg/L. Preferably, the aerosol has an inhalable aerosol drug mass density of between 10 mg/L and 47.5 mg/L. More preferably, the aerosol has an inhalable aerosol drug mass density of between 15 mg/L and 35 mg/L.
Typically, where the aerosol comprises pyrilamine, the aerosol has an inhalable aerosol drug mass density of between 6 mg/L and 70 mg/L. Preferably, the aerosol has an inhalable aerosol drug mass density of between 13 mg/L and 55 mg/L. More preferably, the aerosol has an inhalable aerosol drug mass density of between 20 mg/L and 40 mg/L.
Typically, where the aerosol comprises hydroxyzine, the aerosol has an inhalable aerosol drug mass density of between 2 mg/L and 100 mg/L. Preferably, the aerosol has an inhalable aerosol drug mass density of between 5 mg/L and 75 mg/L. More preferably, the aerosol has an inhalable aerosol drug mass density of between 10 mg/L and 50 mg/L.
Typically, the aerosol has an inhalable aerosol particle density greater than 106 particles/mL. Preferably, the aerosol has an inhalable aerosol particle density greater than 107 particles/mL. More preferably, the aerosol has an inhalable aerosol particle density greater than 108 particles/mL.
Typically, the aerosol particles have a mass median aerodynamic diameter of less than 5 microns. Preferably, the particles have a mass median aerodynamic diameter of less than 3 microns. More preferably, the particles have a mass median aerodynamic diameter of less than 2 or 1 micron(s).
Typically, the geometric standard deviation around the mass median aerodynamic diameter of the aerosol particles is less than 3.0. Preferably, the geometric standard deviation is less than 2.85. More preferably, the geometric standard deviation is less than 2.7.
Typically, the aerosol is formed by heating a composition containing azatadine, brompheniramine, carbinoxamine, chlorpheniramine, clemastine, cyproheptadine, loratadine, pyrilamine, hydroxyzine, or promethazine to form a vapor and subsequently allowing the vapor to condense into an aerosol.
In a method aspect of the present invention, an antihistamine is delivered to a mammal through an inhalation route. The method comprises: a) heating a composition, wherein the composition comprises at least 5 percent by weight of an antihistamine; and, b) allowing the vapor to cool, thereby forming a condensation aerosol comprising particles, which is inhaled by the mammal. Preferably, the composition that is heated comprises at least 10 percent by weight of an antihistamine. More preferably, the composition comprises 20 percent, 30 percent, 40 percent, 50 percent, 60 percent, 70 percent, 80 percent, 90 percent, 95 percent, 97 percent, 99 percent, 99.5 percent, 99.9 percent or 99.97 percent by weight of an antihistamine.
Typically, the antihistamine is not one of the following antihistamines: dexmedetomidine, diphenhydramine, doxylamine, loratidine, and promethazine.
In certain embodiments, the composition that is heated comprises at least 15 percent by weight of an antihistamine pharmaceutically acceptable salt. Preferably, the salt is a hydrochloric acid salt, hydrobromic acid salt, acetic acid salt, maleic acid salt, formic acid salt or fumaric acid salt.
Typically, the delivered aerosol particles comprise at least 5 percent by weight of an antihistamine. Preferably, the particles comprise at least 10 percent by weight of an antihistamine. More preferably, the particles comprise at least 20 percent, 30 percent, 40 percent, 50 percent, 60 percent, 70 percent, 80 percent, 90 percent, 95 percent, 97 percent, 99 percent, 99.5 percent, 99.9 percent or 99.97 percent by weight of an antihistamine.
Typically, the delivered aerosol has a mass of at least 10 xcexcg. Preferably, the aerosol has a mass of at least 100 xcexcg. More preferably, the aerosol has a mass of at least 200 xcexcg.
Typically, the delivered aerosol particles comprise less than 10 percent by weight of antihistamine degradation products. Preferably, the particles comprise less than 5 percent by weight of antihistamine degradation products. More preferably, the particles comprise less than 2.5, 1, 0.5, 0.1 or 0.03 percent by weight of antihistamine degradation products.
Typically, the particles of the delivered condensation aerosol have a mass median aerodynamic diameter of less than 5 microns. Preferably, the particles have a mass median aerodynamic diameter of less than 3 microns. More preferably, the particles have a mass median aerodynamic diameter of less than 2 or 1 micron(s).
Typically, the geometric standard deviation around the mass median aerodynamic diameter of the aerosol particles is less than 3.0. Preferably, the geometric standard deviation is less than 2.85. More preferably, the geometric standard deviation is less than 2.7.
Typically, the particles of the delivered condensation aerosol comprise less than 90 percent by weight of water. Preferably, the particles comprise less than 80 percent by weight of water. More preferably, the particles comprise less than 70 percent, 60 percent, 50 percent, 40 percent, 30 percent, 20 percent, 10 percent, or 5 percent by weight of water.
Typically, at least 50 percent by weight of the aerosol is amorphous in form, wherein crystalline forms make up less than 50 percent by weight of the total aerosol weight, regardless of the nature of individual particles. Preferably, at least 75 percent by weight of the aerosol is amorphous in form. More preferably, at least 90 percent by weight of the aerosol is amorphous in form.
Typically, the delivered aerosol has an inhalable aerosol particle density greater than 106 particles/mL. Preferably, the aerosol has an inhalable aerosol particle density greater than 107 particles/mL. More preferably, the aerosol has an inhalable aerosol particle density greater than 108 particles/mL.
Typically, the rate of inhalable aerosol particle formation of the delivered condensation aerosol is greater than 108 particles per second. Preferably, the aerosol is formed at a rate greater than 109 inhalable particles per second. More preferably, the aerosol is formed at a rate greater than 1010 inhalable particles per second.
Typically, the delivered aerosol is formed at a rate greater than 0.25 mg/second. Preferably, the aerosol is formed at a rate greater than 0.5 mg/second. More preferably, the aerosol is formed at a rate greater than 1 or 2 mg/second.
Typically, the delivered condensation aerosol results in a peak plasma concentration of the antihistamine in the mammal in less than 1 h. Preferably, the peak plasma concentration is reached in less than 0.5 h. More preferably, the peak plasma concentration is reached in less than 0.2, 0.1, 0.05, 0.02, 0.01, or 0.005 h. (arterial measurement).
Typically, the delivered condensation aerosol is used to treat allergy symptoms.
In another method aspect of the present invention, azatadine, brompheniramine, carbinoxamine, chlorpheniramine, clemastine, cyproheptadine, loratadine, pyrilamine, hydroxyzine, or promethazine is delivered to a mammal through an inhalation route. The method comprises: a) heating a composition, wherein the composition comprises at least 5 percent by weight of azatadine, brompheniramine, carbinoxamine, chlorpheniramine, clemastine, cyproheptadine, loratadine, pyrilamine, hydroxyzine, or promethazine; and, b) allowing the vapor to cool, thereby forming a condensation aerosol comprising particles, which is inhaled by the mammal. Preferably, the composition that is heated comprises at least 10 percent by weight of azatadine, brompheniramine, carbinoxamine, chlorpheniramine, clemastine, cyproheptadine, loratadine, pyrilamine, hydroxyzine, or promethazine. More preferably, the composition comprises 20 percent, 30 percent, 40 percent, 50 percent, 60 percent, 70 percent, 80 percent, 90 percent, 95 percent, 97 percent, 99 percent, 99.5 percent, 99.9 percent or 99.97 percent by weight of azatadine, brompheniramine, carbinoxamine, chlorpheniramine, clemastine, cyproheptadine, loratadine, pyrilamine, hydroxyzine, or promethazine.
In certain embodiments, the composition that is heated comprises at least 15 percent by weight of an azatadine, brompheniramine, carbinoxamine, chlorpheniramine, clemastine, cyproheptadine, loratadine, pyrilamine, hydroxyzine, or promethazine pharmaceutically acceptable salt. Preferably, the salt is a hydrochloric acid salt, hydrobromic acid salt, acetic acid salt, maleic acid salt, formic acid salt or fumaric acid salt.
Typically, the delivered aerosol particles comprise at least 5 percent by weight of azatadine, brompheniramine, carbinoxamine, chlorpheniramine, clemastine, cyproheptadine, loratadine, pyrilamine, hydroxyzine, or promethazine. Preferably, the particles comprise at least 10 percent by weight of azatadine, brompheniramine, carbinoxamine, chlorpheniramine, clemastine, cyproheptadine, loratadine, pyrilamine, hydroxyzine, or promethazine. More preferably, the particles comprise at least 20 percent, 30 percent, 40 percent, 50 percent, 60 percent, 70 percent, 80 percent, 90 percent, 95 percent, 97 percent, 99 percent, 99.5 percent, 99.9 percent or 99.97 percent by weight of azatadine, brompheniramine, carbinoxamine, chlorpheniramine, clemastine, cyproheptadine, loratadine, pyrilamine, hydroxyzine, or promethazine.
Typically, the delivered aerosol has a mass of at least 10 xcexcg. Preferably, the aerosol has a mass of at least 100 xcexcg. More preferably, the aerosol has a mass of at least 200 xcexcg.
Typically, the delivered aerosol particles comprise less than 10 percent by weight of azatadine, brompheniramine, carbinoxamine, chlorpheniramine, clemastine, cyproheptadine, loratadine, pyrilamine, hydroxyzine, or promethazine degradation products. Preferably, the particles comprise less than 5 percent by weight of azatadine, brompheniramine, carbinoxamine, chlorpheniramine, clemastine, cyproheptadine, loratadine, pyrilamine, hydroxyzine, or promethazine degradation products. More preferably, the particles comprise less than 2.5, 1, 0.5, 0.1 or 0.03 percent by weight of azatadine, brompheniramine, carbinoxamine, chlorpheniramine, clemastine, cyproheptadine, loratadine, pyrilamine, hydroxyzine, or promethazine degradation products.
Typically, the particles of the delivered condensation aerosol have a mass median aerodynamic diameter of less than 5 microns. Preferably, the particles have a mass median aerodynamic diameter of less than 3 microns. More preferably, the particles have a mass median aerodynamic diameter of less than 2 or 1 micron(s).
Typically, the geometric standard deviation around the mass median aerodynamic diameter of the aerosol particles is less than 3.0. Preferably, the geometric standard deviation is less than 2.85. More preferably, the geometric standard deviation is less than 2.7.
Typically, the particles of the delivered condensation aerosol comprise less than 90 percent by weight of water. Preferably, the particles comprise less than 80 percent by weight of water. More preferably, the particles comprise less than 70 percent, 60 percent, 50 percent, 40 percent, 30 percent, 20 percent, 10 percent, or 5 percent by weight of water.
Typically, at least 50 percent by weight of the aerosol is amorphous in form, wherein crystalline forms make up less than 50 percent by weight of the total aerosol weight, regardless of the nature of individual particles. Preferably, at least 75 percent by weight of the aerosol is amorphous in form. More preferably, at least 90 percent by weight of the aerosol is amorphous in form.
Typically, where the aerosol comprises azatadine, the aerosol has an inhalable aerosol drug mass density of between 0.2 mg/L and 2.5 mg/L. Preferably, the aerosol has an inhalable aerosol drug mass density of between 0.35 mg/L and 2 mg/L. More preferably, the aerosol has an inhalable aerosol drug mass density of between 0.5 mg/L and 1.5 mg/L.
Typically, where the aerosol comprises clemastine, the aerosol has an inhalable aerosol drug mass density of between 0.25 mg/L and 6 mg/L. Preferably, the aerosol has an inhalable aerosol drug mass density of between 0.35 mg/L and 4 mg/L. More preferably, the aerosol has an inhalable aerosol drug mass density of between 0.5 mg/L and 3.5 mg/L.
Typically, where the aerosol comprises chlorpheniramine, the aerosol has an inhalable aerosol drug mass density of between 0.5 mg/L and 5 mg/L. Preferably, the aerosol has an inhalable aerosol drug mass density of between 0.75 mg/L and 4 mg/L. More preferably, the aerosol has an inhalable aerosol drug mass density of between 1 mg/L and 3 mg/L.
Typically, where the aerosol comprises brompheniramine, carbinoxamine or cyproheptadine, the aerosol has an inhalable aerosol drug mass density of between 0.8 mg/L and 10 mg/L. Preferably, the aerosol has an inhalable aerosol drug mass density of between 1.4 mg/L and 8 mg/L. More preferably, the aerosol has an inhalable aerosol drug mass density of between 2 mg/L and 6 mg/L.
Typically, where the aerosol comprises loratadine, the aerosol has an inhalable aerosol drug mass density of between 2 mg/L and 25 mg/L. Preferably, the aerosol has an inhalable aerosol drug mass density of between 3.5 mg/L and 20 mg/L. More preferably, the aerosol has an inhalable aerosol drug mass density of between 5 mg/L and 15 mg/L.
Typically, where the aerosol comprises promethazine, the aerosol has an inhalable aerosol drug mass density of between 5 mg/L and 60 mg/L. Preferably, the aerosol has an inhalable aerosol drug mass density of between 10 mg/L and 47.5 mg/L. More preferably, the aerosol has an inhalable aerosol drug mass density of between 15 mg/L and 35 mg/L.
Typically, where the aerosol comprises hydroxyzine, the aerosol has an inhalable aerosol drug mass density of between 2 mg/L and 100 mg/L. Preferably, the aerosol has an inhalable aerosol drug mass density of between 5 mg/L and 75 mg/L. More preferably, the aerosol has an inhalable aerosol drug mass density of between 10 mg/L and 50 mg/L.
Typically, where the aerosol comprises pyrilamine, the aerosol has an inhalable aerosol drug mass density of between 6 mg/L and 70 mg/L. Preferably, the aerosol has an inhalable aerosol drug mass density of between 13 mg/L and 55 mg/L. More preferably, the aerosol has an inhalable aerosol drug mass density of between 20 mg/L and 40 mg/L.
Typically, the delivered aerosol has an inhalable aerosol particle density greater than 106 particles/mL. Preferably, the aerosol has an inhalable aerosol particle density greater than 107 particles/mL. More preferably, the aerosol has an inhalable aerosol particle density greater than 108 particles/mL.
Typically, the rate of inhalable aerosol particle formation of the delivered condensation aerosol is greater than 108 particles per second. Preferably, the aerosol is formed at a rate greater than 109 inhalable particles per second. More preferably, the aerosol is formed at a rate greater than 1010 inhalable particles per second.
Typically, the delivered aerosol is formed at a rate greater than 0.25 mg/second. Preferably, the aerosol is formed at a rate greater than 0.5 mg/second. More preferably, the aerosol is formed at a rate greater than 1 or 2 mg/second.
Typically, where the aerosol comprises azatadine, between 0.2 mg and 2.5 mg of azatadine is delivered to the mammal in a single inspiration. Preferably, between 0.35 mg and 2 mg of azatadine is delivered to the mammal in a single inspiration. More preferably, between 0.5 mg and 1.5 mg of azatadine is delivered to the mammal in a single inspiration.
Typically, where the aerosol comprises clemastine, between 0.25 mg and 6 mg of clemastine is delivered to the mammal in a single inspiration. Preferably, between 0.35 mg and 4 mg of clemastine is delivered to the mammal in a single inspiration. More preferably, between 0.5 mg and 3.5 mg of clemastine is delivered to the mammal in a single inspiration.
Typically, where the aerosol comprises chlorpheniramine, between 0.5 mg and 5 mg of chlorpheniramine is delivered to the mammal in a single inspiration. Preferably, between 0.75 mg and 4 mg of chlorpheniramine is delivered to the mammal in a single inspiration. More preferably, between 1 mg and 3 mg of chlorpheniramine is delivered to the mammal in a single inspiration.
Typically, where the aerosol comprises brompheniramine, carbinoxamine or cyproheptadine, between 0.8 mg and 10 mg of brompheniramine, carbinoxamine or cyproheptadine is delivered to the mammal in a single inhalation. Preferably, between 1.4 mg and 8 mg of brompheniramine, carbinoxamine or cyproheptadine is delivered to the mammal in a single inhalation. More preferably, between 2 mg and 6 mg of brompheniramine, carbinoxamine or cyproheptadine is delivered to the mammal in a single inhalation.
Typically, where the aerosol comprises loratadine, between 2 mg and 25 mg or loratadine is delivered to the mammal in a single inhalation. Preferably, between 3.5 mg and 20 mg of loratadine is delivered to the mammal in a single inspiration. More preferably, between 5 mg and 15 mg of loratadine is delivered to the mammal in a single inspiration.
Typically, where the aerosol comprises promethazine, between 5 mg and 60 mg of promethazine is delivered to the mammal in a single inspiration. Preferably, between 10 mg and 47.5 mg of promethazine is delivered to the mammal in a single inspiration. More preferably, between 15 mg and 35 mg of promethazine is delivered to the mammal in a single inspiration.
Typically, where the aerosol comprises hydroxyzine, between 2 mg and 100 mg of hydroxyzine is delivered to the mammal in a single inspiration. Preferably, between 5 mg and 75 mg of hydroxyzine is delivered to the mammal in a single inspiration. More preferably, between 10 mg and 50 mg of hydroxyzine is delivered to the mammal in a single inspiration.
Typically, where the aerosol comprises pyrilamine, between 6 mg and 70 mg of pyrilamine is delivered to the mammal in a single inspiration. Preferably, between 13 mg and 55 mg of pyrilamine is delivered to the mammal in a single inspiration. More preferably, between 20 mg and 40 mg of pyrilamine is delivered to the mammal in a single inspiration.
Typically, the delivered condensation aerosol results in a peak plasma concentration of azatadine, brompheniramine, carbinoxamine, chlorpheniramine, clemastine, cyproheptadine, loratadine, pyrilamine, hydroxyzine, or promethazine in the mammal in less than 1 h. Preferably, the peak plasma concentration is reached in less than 0.5 h. More preferably, the peak plasma concentration is reached in less than 0.2, 0.1, 0.05, 0.02, 0.01, or 0.005 h. (arterial measurement).
Typically, the delivered condensation aerosol is used to treat allergy symptoms.
In a kit aspect of the present invention, a kit for delivering an antihistamine through an inhalation route to a mammal is provided which comprises: a) a composition comprising at least 5 percent by weight of an antihistamine; and, b) a device that forms an antihistamine containing aerosol from the composition, for inhalation by the mammal. Preferably, the composition comprises at least 10 percent by weight of an antihistamine. More preferably, the composition comprises at least 20 percent, 30 percent, 40 percent, 50 percent, 60 percent, 70 percent, 80 percent, 90 percent, 95 percent, 97 percent, 99 percent, 99.5 percent, 99.9 percent or 99.97 percent by weight of an antihistamine.
Typically, the device contained in the kit comprises: a) an element for heating the antihistamine composition to form a vapor; b) an element allowing the vapor to cool to form an aerosol; and, c) an element permitting the mammal to inhale the aerosol.
In another kit aspect of the present invention, a kit for delivering azatadine, brompheniramine, carbinoxamine, chlorpheniramine, clemastine, cyproheptadine, loratadine, pyrilamine, hydroxyzine, or promethazine an inhalation route to a mammal is provided which comprises: a) a composition comprising at least 5 percent by weight of azatadine, brompheniramine, carbinoxamine, chlorpheniramine, clemastine, cyproheptadine, loratadine, pyrilamine, hydroxyzine, or promethazine; and, b) a device that forms a azatadine, brompheniramine, carbinoxamine, chlorpheniramine, clemastine, cyproheptadine, loratadine, pyrilamine, hydroxyzine, or promethazine containing aerosol from the composition, for inhalation by the mammal. Preferably, the composition comprises at least 10 percent by weight of azatadine, brompheniramine, carbinoxamine, chlorpheniramine, clemastine, cyproheptadine, loratadine, pyrilamine, hydroxyzine, or promethazine. More preferably, the composition comprises at least 20 percent, 30 percent, 40 percent, 50 percent, 60 percent, 70 percent, 80 percent, 90 percent, 95 percent, 97 percent, 99 percent, 99.5 percent, 99.9 percent or 99.97 percent by weight of azatadine, brompheniramine, carbinoxamine, chlorpheniramine, clemastine, cyproheptadine, loratadine, pyrilamine, hydroxyzine, or promethazine.
Typically, the device contained in the kit comprises: a) an element for heating the azatadine, brompheniramine, carbinoxamine, chlorpheniramine, clemastine, cyproheptadine, loratadine, pyrilamine, hydroxyzine, or promethazine composition to form a vapor; b) an element allowing the vapor to cool to form an aerosol; and, c) an element permitting the mammal to inhale the aerosol.